CN107076737B

CN107076737B - Flexible integrated urine-based diagnostic device

Info

Publication number: CN107076737B
Application number: CN201580033104.5A
Authority: CN
Inventors: E·贝萨妮; F·迪梅尔
Original assignee: Lia Diagnostics Inc
Current assignee: Lia Diagnostics Inc
Priority date: 2014-05-11
Filing date: 2015-05-07
Publication date: 2020-03-17
Anticipated expiration: 2035-05-07
Also published as: AU2015259567A1; CA2957066A1; EP3143402A1; KR102446454B1; US10542886B2; JP2017519225A; WO2015175301A8; CN107076737A; US9606116B2; US20180344159A1; WO2015175301A1; EP3143402A4; MX2016014769A; JP6786478B2; KR20170055936A; CN111239388A; IL248820A0; AU2015259567B2; US20170280999A1; DK3143402T3

Abstract

A flexible, integrated, urine-based diagnostic device designed such that one or more diagnostic channels are integrated into the body of the device. Each diagnostic channel is designed to contain an immunoassay to detect the presence of a selected analyte so that the device can return a visible readout indicating the presence of the analyte. The flexibility of the device aids the user in the sample collection process.

Description

Flexible integrated urine-based diagnostic device

Cross Reference to Related Applications

This application claims priority to U.S. provisional patent application No. 61/996,978, filed on 11/5/2014. The contents of this application are incorporated by reference herein in their entirety.

Background

Diagnostic devices based on urine in its general form are used in both the home and clinical settings for men and women to test for a variety of physical conditions and analytes that may be present in urine and other bodily fluids. The device has been developed to provide rapid, accurate and easy to use testing to untrained people in the field.

Existing devices typically include at least two parts: a rigid structure serving as a support for the device, and a test strip for performing the test itself. Such devices use rigid body structures, imprecise sample collection methods (sometimes requiring counting from the user), separate abstract readout of each test strip (in non-electronic devices), and implicit landfill disposal. Urine-based diagnostics generally fall into the categories of mesostreaming (devices held in a flowing stream of fluid), dipping (devices held in a stationary fluid sample), and cartridges (pipettes are used to add fluid samples).

The increasing popularity and complexity of these devices has led to a number of problems. Those skilled in the art will appreciate that a test format is still desirable that integrates the entirety of the device (including the user interface, the collection portion, and the test portion) into a single format. This will help to simplify the manufacturing process and improve the ease of use of the device. Furthermore, the increase in complexity of existing devices enables such devices to give an electronic readout of the result at the expense of increased cost and battery operation requirements. It will be appreciated by those skilled in the art that a test format in which the device is capable of giving both a positive index (indicator) and a negative index without the use of electronic components is still desirable. This solution would be particularly important as it facilitates the user experience, reduces costs, simplifies manufacturing, and avoids the use of expensive and non-biodegradable electronic components. The user experience can be even further improved by using a visual readout with a clearer indication than current non-electronic devices in the market, which typically use one or more lines to indicate results that are often difficult to interpret.

Since these diagnostic devices are often used to obtain sensitive test results, it is often an important priority for the user to be free to handle. There are many ways to improve the free handling of the test. In order to be freely disposed of when carrying the device, it is desirable to form a device that is not only small, but also can be folded into a compact form without damaging the device itself. Furthermore, in cases where it is not desirable for the device to be discovered, it may be particularly important that it can be freely disposed of. Therefore, a completely water-flushable or water-dispersible test format would be advantageous. A water flushable, water dispersible, or biodegradable device would also be desirable as it would reduce the dependence on landfill systems.

Ease of use is also important for these types of in-home testing devices that are typically used by untrained people. Typical hand-held devices are rigid and require aiming of urine at the user's site, which is often particularly difficult for women. Other devices in the art attempt to address this problem by allowing the user to dip the test portion into the sample or attach the device to a toilet. One skilled in the art will recognize that it would be beneficial to simplify the user experience to be able to facilitate sample collection and testing without first collecting the sample in a separate container or without attaching the device to the subject to be collected.

Disclosure of Invention

The present invention is directed to a urine-based diagnostic test and testing device that addresses the above-mentioned and other needs in the art. One embodiment of the device is designed to form a single integrated testing device comprising a user interface, a collecting section and a testing section, which increases the manufacturing simplicity and ease of use of the device. In this embodiment, one or more diagnostic channels are integrated into the device material. Each diagnostic channel includes an immunoassay for reacting with an analyte in a sample. Furthermore, the device itself is flexible so that it can be adjusted to assist in collecting urine.

Other embodiments of the device include one or more channels having a sandwich immunoassay, a competitive immunoassay, or both a competitive and a sandwich immunoassay. In other embodiments, competitive and sandwich immunoassays are capable of giving a positive or negative visual readout to the user. Other embodiments of the device may be flushable, water dispersible, or biodegradable to reduce dependence on landfills and to help maintain undiscovered test results. In other embodiments, the device may also be foldable to help keep the device out of sight and to help transport the product. In other embodiments, the readout of the device is displayed by text, graphical design, or symbols to facilitate ease of use. Other embodiments of the device may also include an embossed pattern on the collection portion of the device to aid in the collection of the sample and to direct the flow of the sample. In further embodiments, the collection portion of the device includes perforations so that contaminated portions of the device can be removed after sample collection without affecting the test results.

Drawings

The above and other advantageous features of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a perspective view of one embodiment of an apparatus including a volume indicator, a positive value indicator, a control indicator, a tear line, and an embossed collection pad.

FIG. 2 is a perspective view of one embodiment of a device in which two immunoassays are integrated into the device to give either a positive or negative reading.

Figure 3 is a perspective view of one embodiment of a device including a positive readout, a control indicator, a volume indicator, an embossed collection area, and two fold lines.

FIG. 4 is a perspective view of a portion of one embodiment of a device in which test results are given using written language reading.

FIG. 5 is a side view of one embodiment of the device with the device opened flat.

FIG. 6 is a side view of one embodiment of the device with the device folded in the middle.

Figure 7 is a side view of one embodiment of the device wherein the device is fully collapsed.

FIG. 8 is a perspective view of an embodiment of a device including a controller, a first immunoassay, a second immunoassay, and a third immunoassay, a volume indicator, two fold lines, and an embossed collection pad in the same lane.

Fig. 9 is a perspective view of an embodiment of the device in which test results are given using a graphical design.

Detailed Description

Various embodiments of the present invention are designed as an integrated diagnostic device in which the structure, user interface, collection portion and testing portion form a single easy-to-use and easy-to-manufacture testing device.

One embodiment of the apparatus is shown in fig. 1. This embodiment is an integrated device comprising a diagnostic channel with an immunoassay 1, a urine volume indicator 2, a control indicator 3, perforations 4 and an embossed collection pad 5. In one embodiment, the device uses microfluidic technology as a channel system for diagnostic assays, which allows the channel system to be a single manufactured object with a user interface and structure. The device integrates these attributes into a single material, integrating the components that the user holds, uses, or urinates onto with the microfluidic channels and diagnostic assays. The arrangement of immunoassay 1, urine volume indicator 2 and control indicator 3in fig. 1 is not the only one contemplated and should not be limited to such an arrangement. A control indicator 3 is included to provide a visual indication that the test has run.

In the embodiment shown in fig. 1, the immunoassay may be designed to test for a variety of analytes. For example, in one embodiment, the immunoassay may be designed to test the hormone hCG, which will allow the device to return a result as to whether the user is pregnant. However, the device can be designed to test for any number of analytes present in urine, including but not limited to hCG-H and various drugs (such as cocaine, THC, or amphetamines), glucose, ketones, luteinizing hormone, or hemoglobin. Depending on the analyte selected, the device may be designed to test for various medical conditions, diseases, or other information, including the presence of a transmitted disease, diabetes, pregnancy, kidney disease, or cancer.

The immunoassay used in the various embodiments may be designed in a number of different ways. For example, immunoassays can be designed as "sandwich" assays or "competitive" assays. In addition, immunoassays can be constructed to perform the test in a lateral flow or vertical flow format. The type of assay used will depend on the desired function of the device. For example, one skilled in the art will recognize that if a device is required to indicate that an analyte is present at a concentration above a predetermined concentration, a "sandwich" assay would be useful, while a "competitive" assay would indicate when the desired analyte is not present at a predetermined level.

The immunoassay can be adhered to the nonwoven material of the device in a variety of ways. A simple way to achieve this is to add a mixture of the biorecognition agent directly to the device in the desired form and then dry the mixture to adhere it to the device. The biorecognition agent depends on the analyte being tested for and may include detecting antibodies, hormones or other chemicals that target the analyte. This method of drying the antibody to the device has the added benefit of simplicity. However, other methods, such as various printing techniques, may be used. One example is the use of ink jet printing, which one of ordinary skill in the art will find useful because it is a non-impact technique, among other reasons. One example of inkjet printing that can be used is by using Sol-Gel (Sol-Gel). See, e.g., Jinnyun Wang et al, Morphology and encapsulated Enzyme Performance in Inkjet-Printed Sol-Gel Coatings on Paper, 26chem.Mater.1941(2014), which is incorporated herein by reference. However, other application techniques of sol-gel may be used, such as dot-matrix printing, screen printing, coating, automatic pipetting, stamping or spraying.

These immunoassay channels can also be generated in a variety of ways. A simple method for creating channels is by using an impact technique, wherein indentations are created in the material to which an immunoassay can be added. In these embossing techniques, the indentations form channels that direct the flow of liquid through to the immunoassay. Furthermore, embossing techniques can be used to create a barrier by varying the density of the device material, thereby creating a more dense hydrophobic channel wall that directs the flow of sample through the channel. Another way in which the channels may be formed is by a printing process. For example, in some embodiments, an inkjet printable sol-gel material may be used to form a hydrophobic barrier for these channels. See, for example, Jungyun Wang et al, Morphology and applied enzyme Performance in Inkjet-Printed Sol-Gel Coatings on Paper, 26chem.Mater.1941 (2014).

Those skilled in the art will recognize the many advantages of integrating the test channels and immunoassays into the device itself. This technique avoids the use of nitrocellulose test strips used in many devices on the market. By avoiding the use of nitrocellulose test strips and integrating the entire device into a single material, the manufacturing process is simplified. Furthermore, nitrocellulose test strips are not flushable, which is a significant obstacle to the formation of fully flushable test strips.

In the embodiment shown in fig. 1, urine volume indicator 2 provides a visual indication of the adequacy of the sample. Those skilled in the art will recognize that this feature is advantageous for a way of indicating volume adequacy in existing applications where a user desires to count anywhere from 5 seconds to 30 seconds in his or her head to know when the device has an adequate volume of fluid sample. Having the volume indicator 2 integrated into the device also avoids the use of electronics within the device to indicate when a sufficient fluid level is achieved. There are also devices that have color changing properties to indicate that the device is in contact with a fluid, but such devices do not indicate whether the proper volume is achieved. The volume indicator 2 in fig. 1 can be implemented in a number of ways, including by using the wetness-sensitive color-changing ink portion as part of a urine-based diagnostic device designed to accomplish its wetness-sensitive color-changing transition when a sufficient urine fluid sample is obtained for optimally performing a diagnosis. The humidity sensitive color changing ink reacts with the fluid by changing the appearance of its color. In some embodiments, this design for the device may be linear and communicate as part of the user interface. Its transition from one color to another will serve as a visual tool for the user to indicate that a satisfactory amount of the fluid sample is on and within the diagnostic device. While the wetness sensitive color-changing ink may be used in the preferred embodiment of the device, other volume indicators may be used, including wetness sensitive color-changing coatings, color measurements, acid/base reactivity tests, dispensing of ink or paint when wetted, testing the appearance of an element when wetted or by using a chemically sensitive material when the material becomes translucent or transparent. One example of a chemically sensitive material is the use of humidity sensitive nanofibers. See, for example, Mogera, U.S. et al, Ultrafast Response noise Sensor using in random molecular Nanofibre and its Application in Monitoring Breath noise Flow,4Sci. Rep.4103(2014), which is incorporated herein by reference.

The embodiment shown in fig. 1 also comprises perforations 4. The perforation is designed such that contaminated parts of the device for collecting a sample can be discarded by the user while waiting for the result without affecting the read-out. Those skilled in the art will recognize that this is advantageous for a number of reasons, including reducing the test size to be discarded to aid flushability, and allowing the user to discard the contaminated portion of the device for hygienic reasons while waiting for the results.

The embodiment of fig. 1 also includes an embossed collection pad 5. The collection pad 5 is designed to increase the surface area of the collection portion of the device and to facilitate the flow of sample to the testing portion of the device. To increase the flow to the testing part of the device, it would be advantageous for the channels in the imprinted pattern to be oriented vertically, i.e. parallel to the immunoassay channels. However, the imprint pattern can be designed in a number of ways to adjust the time it takes for the sample to reach the channel. By adjusting the imprint pattern, the device can be designed to return a fast result without moving the sample so fast that it washes the biological identifiers in the immunoassay. In this way, the speed at which the device returns results can be controlled.

In other embodiments of the invention, all of the devices are flushable or water dispersible, which provides an optional privacy layer for users who do not wish to have their results enter a landfill or to recycle the associated municipal waste system. The flushability is determined by the shape and material of the device, but there are many combinations of the two. The constraint of the device can be characterized as being small enough in depth and width to pass through all standard pipes. In an exemplary embodiment, the material is formed from cellulose fibers in a compressed or non-woven format, and may include a binder material, such as polyvinyl alcohol, although other types of materials may also be used. The nonwoven format can be formed by a number of different processes, including wet-laid or air-laid operations. Wet laid and air laidNonwoven technology is well known in the art. See, for example, EP0321237B1, which is incorporated herein by reference. Furthermore, the cellulose pulp fibers may be hydroentangled in order to prevent degradation of the device during use, while still maintaining flushability. However, while cellulose blends are preferred, the invention is not limited to such materials, so long as the material selected meets the flushable requirements. One such suitable material for use in the present application is available from Suominen Corporation under the trade name HYDRASPUN^TMAnd (4) obtaining. The composition should meet the requirement of 8 months in 2013

2013 evaluation of flushability guidelines for disposable nonwoven products in third edition of INDA and EDANA: standards and Guidelines specified in the procedure for Assessing the Compatibility of disposable nonwoven Products with piping and Wastewater infrastructure (Guidelines for assembling the usability of disposable on nonwoven Products: A Process for assembling the Compatibility of disposable on nonwoven Products with the plus binding and Water in the construction. third edition. August 2013.

2013INDA and DEANA)。

In another embodiment of the invention, the device may be adjustable or flexible for user interaction and personalization, packaging and transportation purposes. Those skilled in the art will recognize that in order for a female user to leave the intermediate urine on the diagnostic device, some degree of targeting of the user's site is required, thereby creating the possibility of user site misuse or confusion. In culture, women do not want to aim their urine stream in many cases, and flexible solutions provide the opportunity for user adjustment and user personalization to adapt to the flow and directionality of their urine stream. The act of collecting urine through the midstream device can be simplified by a more dynamic design that allows greater user control. The flexibility of the device can be adjusted based on the material used. For example, the nonwoven material may be made more or less flexible based on the manner in which the fibers are combined, the manner in which the material is made, and the additives added to the cellulosic material. More specifically, the increased stiffness of the nonwoven material can be achieved by a variety of methods including, but not limited to, compression molding or addition of water-dispersible stiffening agents, such as wet strength resins. In some embodiments, the device may be highly flexible, while in other embodiments, the device may be more rigid in nature. For example, based on the nonwoven material or technique used, the device can be designed to be adjusted by the user or others into a desired form prior to use, whereby the device can retain its shape during sample collection. In this way, the form of the device can be personalized to the user.

In another embodiment of the invention, the device is foldable. By being foldable, the device can be more easily packaged and transported. Furthermore, the foldable device facilitates free handling, as it may reduce the size of the device allowing independent carrying. A foldable embodiment of the device is shown in fig. 5, 6 and 7. In these examples, the device has two fold lines 13, so that the surface area of the device can be reduced for more individual carrying and packaging. However, any number of fold lines may be present depending on what dimensions are required for the folded device. Furthermore, the integration of the device into a single material allows the collapsible properties to be possible without affecting the integrity of the device.

Figure 2 depicts another embodiment of the device, wherein the device utilizes a "conventional" or "sandwich" assay 7 and a "competitive" assay 8 and a volume indicator 6. The "conventional" or "sandwich" assay 7 is used to display a color visual readout when the specified element or hormone is present. These can take many formats, including lateral flow or vertical flow tests. It will be appreciated by those skilled in the art that such conventional assays, also known as enzyme-linked immunosorbent assays (ELISAs), are commonly used in current test devices, such as many pregnancy test kits currently on the market. In this conventional assay, a biorecognition agent is used to bind to a selected analyte to give a visual readout when the selected analyte is present at a predetermined concentration. In this case, if the specified element or hormone is not present, a color visual readout will not occur. In the "competitive" assay 8, this situation is reversed from the user's perspective. Including another phase of the assay, which contains a form of the specified element or hormone with conjugating enzyme. If the specified element or hormone is present in the collected urine sample, the specified element or hormone may travel through the channel of the assay "competing" with the modifying element that has the conjugated enzyme of the antibody for binding. In this case no color change occurs and no visual readout is shown to the user. If the designated element or hormone is not present in the collected urine sample, the modified element with conjugating enzyme will not have "competition" for the antibody for binding and will produce a visual readout of the color change for the user. This embodiment of the invention includes the feature of allowing both types of assays to be co-located in a single urine-based diagnostic device. An example of this is that in a pregnancy test, a pregnant woman will obtain a visual diagnostic readout indicating the presence of the hormone hCG (human chorionic gonadotropin), while a non-pregnant woman will also obtain a visual diagnostic readout indicating the absence of hCG.

Fig. 8 depicts another embodiment in which the device utilizes the controller 14, the first immunoassay 15, the second immunoassay 16 and the third immunoassay 17, the volume indicator 18, the two fold lines 19 and the embossed collection pad 20 in the same channel. In this embodiment, the plurality of immunoassays are configured to test for different analytes. For example, a first immunoassay may be designed to detect a predetermined level of hCG, a second immunoassay may be designed to detect a predetermined level of glucose, and a third immunoassay may be designed to detect luteinizing hormone. In this way, the device can test for the presence of three different analytes using a single sample. However, this embodiment of the invention is not limited to this number of immunoassays or these analytes. The device may be configured with multiple immunoassays to test for any number of analytes in order to give the desired number and type of results.

In further embodiments, multiple immunoassays may be designed to test multiple levels of analyte. For example, the device may be configured with three immunoassays, each testing a different concentration of hCG, such as 25,000mIU/ml, 7,000mIU/ml and 25 mIU/ml. In this example, the device may indicate not only a positive result of pregnancy, but also an approximate time period that the user is pregnant. By testing multiple volumes of analyte, the user may also be given an approximate range of analyte amounts in the sample. The number of immunoassays and the level of testing used in the device may vary based on what type of information the device needs to return-a higher number of immunoassay tests can return a more accurate estimate of the target analyte volume in the sample for smaller analyte volume intervals.

Fig. 3 depicts another embodiment of the device using a control indicator 9, a positive value readout 10, a volume indicator 11, an embossed collection area 12 and a fold line 13. In this embodiment the control indicator 9 and the positive value readout 10 are located in a linear arrangement. The volume indicator 11 is designed to allow the user to know when a sufficient sample volume has been obtained. The embossed collection pad 12 helps to direct the flow to the channel. The fold line 13 enables the user to fold the device to a smaller size for easier and more discrete carrying.

Fig. 4 depicts another embodiment of the apparatus in which the diagnostic readout is represented using words or language. Those skilled in the art will recognize that this increases the level of clarity and ease of use compared to existing devices that rely on lines, squares or patterns, or provide reading of written language on electronic materials. The device includes features that allow the non-electronic device to have a word or language read of the diagnostic result. The microfluidic channel is designed in such a way that the colour-changing part of the diagnostic assay is positioned in a word-like pattern. One example is that the device has antibodies in the designed channels so that pregnancy can be indicated by the word "pregnancy" if the diagnosis is positive.

Fig. 9 depicts another embodiment of an apparatus in which a visual readout is displayed using a graphical design or other graphical representation. By using a recognizable graphical representation of the test results, the ease of use of the device is enhanced. The design achieved by designing the microfluidic channels is the shape of the desired pattern. In the embodiment shown in fig. 9, the device utilizes the face of the infant to indicate a positive pregnancy test result. However, other graphs or illustrations may be used based on what type of analyte the device is configured to detect.

Various embodiments of the present invention are designed for untrained persons (but not limited to use by such persons) to use the device to test a selected analyte or physical condition. The user of the device, after adjusting his flexible form to assist in sample collection, can add a urine sample to the collection portion of the device by urinating directly onto the device. The sample may then travel through the testing portion of the device before the device returns a visual result.

Claims

1. A flexible, integrated diagnostic test device for testing urine, comprising:

a body formed of a flexible material configured to be adjustable to facilitate collection of urine;

one or more diagnostic channels positioned in the body, each diagnostic channel comprising at least one immunoassay reagent configured to bind to at least one analyte in a urine sample; and

a visual indicator positioned in the body configured to indicate at least one of a presence or an absence of the at least one analyte in the sample;

wherein the entire flexible integrated diagnostic test device is water dispersible.

2. The device of claim 1, wherein the at least one immunoassay reagent comprises a sandwich immunoassay reagent configured to indicate the presence of the at least one analyte at a predetermined concentration.

3. The device of claim 1, wherein the at least one immunoassay reagent comprises a competitive immunoassay reagent configured to indicate that the at least one analyte is not present at the predetermined concentration.

4. The device of claim 1, wherein the at least one immunoassay reagent comprises a sandwich immunoassay reagent adapted to indicate the presence of the at least one analyte at a predetermined concentration, and the at least one immunoassay reagent comprises a competitive immunoassay reagent adapted to indicate the absence of the at least one analyte at the predetermined concentration.

5. The device of claim 1, wherein at least two immunoassay reagents are configured to each bind to a different analyte, and wherein the visual indicator is configured to provide an indication of at least one of the presence or absence of the plurality of analytes in the urine sample.

6. The device of claim 1, wherein at least two immunoassay reagents are configured to detect different concentrations of at least one analyte, and the visual indicator is configured to provide an indication of the presence or absence of the at least one analyte at the different concentrations.

7. The device of claim 1, wherein the device is foldable.

8. The device of claim 1, wherein the entire diagnostic test device is formed of a water-flushable material.

9. The device of claim 8, wherein the entire diagnostic test device is biodegradable.

10. The device of claim 8, wherein the body is comprised of non-woven cellulose.

11. The device of claim 1, further comprising a visible marker configured to indicate the presence of a predetermined minimum volume of the urine sample sufficient for testing the urine sample.

12. The device of claim 11, wherein the visible indicia comprises a humidity sensitive color-changing ink configured to change color when contacted to the predetermined minimum volume of the urine sample.

13. The device of claim 1, wherein the visual indicator comprises a microfluidic channel configured to display text indicating at least one of the presence or absence of at least one analyte at a predetermined concentration of the at least one analyte.

14. The device of claim 1, wherein the visual indicator comprises a microfluidic channel configured to display at least one of a graphical design or a graphical representation indicating at least one of a presence or an absence of the at least one analyte at a predetermined concentration of the at least one analyte.

15. The device of claim 1, further comprising a perforation between the collection portion and the test portion of the device, and wherein the collection portion is separated from the test portion at the perforation.

16. The apparatus of claim 1, further comprising an embossed pattern.

17. A diagnostic test device for testing a urine sample, comprising:

a main body; and

a plurality of diagnostic channels integrated into the body, each diagnostic channel comprising immunoassay reagents for reacting with at least one analyte in a urine sample, wherein at least one sandwich immunoassay reagent and one competitive immunoassay reagent are present;

wherein the entire diagnostic test device is water dispersible.

18. The device of claim 17, wherein the device is foldable.

19. A diagnostic test device for testing a urine sample, comprising:

a flexible, collapsible and flushable body;

one or more diagnostic channels integrated into the body;

a plurality of immunoassay reagents disposed within one or more diagnostic channels, the plurality of immunoassay reagents configured to react with at least one analyte in the urine sample; and

a visual indicator integrated into the body configured to indicate at least one of a presence or absence of at least one analyte at a predetermined concentration of the at least one analyte;

wherein the entire diagnostic test device is water dispersible.

20. The device of claim 1, wherein the entire diagnostic test device is constructed of a single water-dispersible material.